Project Summary/Abstract: Core C The goal of Core C is to develop an extensive, clinically annotated patient-derived xenograft bank for Ewing sarcoma. These PDX models will be extensively characterized using state-of-the-art genomic approaches (DNAseq RNAseq, single cell RNAseq, subclonal analysis). Models will also be rigorously evaluated for Ewing sarcoma phenotypes of clinical relevance (ability to form metastasis in subcutaneous and tail vein injection assays, response to standard chemotherapy agents, etc). We will enable the use of these models for CRISPR and other functional approaches. Core C will interact closely with the three Projects and the other cores. A central deliverable of Core C will be evaluation of new therapeutic opportunities developed through Projects 1- 3. We anticipate that Core C will serve as a paradigm for preclinical studies for a wide range of pediatric sarcomas.